Single group VBM analysis with additional covariates (PCs): the statistical map represents the correlation between PC2 and GM volume in AS children overlaid on the study-specific grey matter template (created by FSL-VBM protocol) on the sagittal, coronal and axial plane.

<p>Single group VBM analysis with additional covariates (PCs): the statistical map represents the correlation between PC2 and GM volume in AS children overlaid on the study-specific grey matter template (created by FSL-VBM protocol) on the sagittal, coronal and axial plane.</p

A chart of the correlation matrix.

<p>The distribution of each variable is shown on the diagonal. On the bottom of the diagonal: the bivariate scatter plots with a fitted line are displayed. On the top of the diagonal: the value of the correlation plus the significance level as stars. Abbreviations: CSF, cerebrospinal fluid; GM, grey matter; WM, white matter; PC, principal component.</p

Table_3_Recombinant FSH Improves Sperm DNA Damage in Male Infertility: A Phase II Clinical Trial.DOCX

<p>Background and objectives: Male infertility is a global health dilemma and Follicle-Stimulating Hormone (FSH) administration has shown promising results. Several studies showed that infertile men with normal semen parameters have low levels of DNA damage while infertile men with abnormal semen parameters have more damage at the DNA level. Sperm DNA damage may affect the reproductive outcome and has been associated with failure in the achievement of competent embryos and pregnancy fulfillment. The aim of this study was to evaluate whether the administration of recombinant FSH (Gonal-f® PEN 900 IU) could improve sperm DNA fragmentation in men with infertility. The secondary endpoints of this study were to evaluate the FSH effects on sperm parameters and hormonal assets.</p><p>Methods: A longitudinal, prospective, multicenter, open-label clinical trial was carried out. Infertile couples were recruited from six Italian Reproductive Medical Centers and 115 infertile men were enrolled for this study. All participants were treated with subcutaneous injections of Gonal-f® 150 IU every other day, within a 3 month-time frame. The semen samples were examined in accordance to the 2010 World Health Organization criteria. Sperm DNA Fragmentation (DFI) was determined by fluorescence microscopy using terminal deoxynucleotidyl transferase-mediated d-UTP Nick-end Labeling (TUNEL) assay. Statistical analysis was performed using both the t-test for paired samples and the Wilcoxon signed-rank test.</p><p>Results: FSH administration improved DFI in 67% of patients, with an average decrease of 35.4% compared to the baseline. This improvement is more evident in men with basal DFI lower than 17% and in those with FSH basal levels between 2.16 and 4.27 IU/L. In addition, FSH enhanced the gonadal function, increasing the hormones AMH and Inhibin B and semen parameters. Limitation of these results are represented by the absence of a placebo group and of FSHR genotype stratification sub-analysis.</p><p>Conclusion: Recombinant FSH 150 IU is well tolerated and effective in eliciting a significant DFI reduction as well as in improving gonadal function.</p><p>Trial Registration: EUDRACT Number 2010-020196-23. Registred 14 April 2011.</p

The coefficients for the first three principle components and the variance explained.

<p>The coefficients for the first three principle components and the variance explained.</p

Between-group VBM analysis: the statistical map is overlaid on the study-specific grey matter template (created by FSL-VBM protocol) on axial plane.

<p>Red-yellow clusters show grey matter volumetric reduction in children with Angelman syndrome compared to controls.</p

The two-dimensional biplot shows the projection of the data on the first two PCs.

<p>It colors each point according to the gender and shows the loading of each variable on the first two principal components with a circle of correlation.</p

Size and labelled anatomical structures of the significant clusters (p < 0.05, corrected).

<p>The voxel coordinates (in millimeter) in MNI standard space for the location of the maximum intensity are presented. The probability values are scaled from 0 to 100 and indicate the probability of the cluster being a member of the different labelled regions within the atlas.</p

Table_1_Recombinant FSH Improves Sperm DNA Damage in Male Infertility: A Phase II Clinical Trial.DOCX

<p>Background and objectives: Male infertility is a global health dilemma and Follicle-Stimulating Hormone (FSH) administration has shown promising results. Several studies showed that infertile men with normal semen parameters have low levels of DNA damage while infertile men with abnormal semen parameters have more damage at the DNA level. Sperm DNA damage may affect the reproductive outcome and has been associated with failure in the achievement of competent embryos and pregnancy fulfillment. The aim of this study was to evaluate whether the administration of recombinant FSH (Gonal-f® PEN 900 IU) could improve sperm DNA fragmentation in men with infertility. The secondary endpoints of this study were to evaluate the FSH effects on sperm parameters and hormonal assets.</p><p>Methods: A longitudinal, prospective, multicenter, open-label clinical trial was carried out. Infertile couples were recruited from six Italian Reproductive Medical Centers and 115 infertile men were enrolled for this study. All participants were treated with subcutaneous injections of Gonal-f® 150 IU every other day, within a 3 month-time frame. The semen samples were examined in accordance to the 2010 World Health Organization criteria. Sperm DNA Fragmentation (DFI) was determined by fluorescence microscopy using terminal deoxynucleotidyl transferase-mediated d-UTP Nick-end Labeling (TUNEL) assay. Statistical analysis was performed using both the t-test for paired samples and the Wilcoxon signed-rank test.</p><p>Results: FSH administration improved DFI in 67% of patients, with an average decrease of 35.4% compared to the baseline. This improvement is more evident in men with basal DFI lower than 17% and in those with FSH basal levels between 2.16 and 4.27 IU/L. In addition, FSH enhanced the gonadal function, increasing the hormones AMH and Inhibin B and semen parameters. Limitation of these results are represented by the absence of a placebo group and of FSHR genotype stratification sub-analysis.</p><p>Conclusion: Recombinant FSH 150 IU is well tolerated and effective in eliciting a significant DFI reduction as well as in improving gonadal function.</p><p>Trial Registration: EUDRACT Number 2010-020196-23. Registred 14 April 2011.</p

Table_2_Recombinant FSH Improves Sperm DNA Damage in Male Infertility: A Phase II Clinical Trial.DOCX

<p>Background and objectives: Male infertility is a global health dilemma and Follicle-Stimulating Hormone (FSH) administration has shown promising results. Several studies showed that infertile men with normal semen parameters have low levels of DNA damage while infertile men with abnormal semen parameters have more damage at the DNA level. Sperm DNA damage may affect the reproductive outcome and has been associated with failure in the achievement of competent embryos and pregnancy fulfillment. The aim of this study was to evaluate whether the administration of recombinant FSH (Gonal-f® PEN 900 IU) could improve sperm DNA fragmentation in men with infertility. The secondary endpoints of this study were to evaluate the FSH effects on sperm parameters and hormonal assets.</p><p>Methods: A longitudinal, prospective, multicenter, open-label clinical trial was carried out. Infertile couples were recruited from six Italian Reproductive Medical Centers and 115 infertile men were enrolled for this study. All participants were treated with subcutaneous injections of Gonal-f® 150 IU every other day, within a 3 month-time frame. The semen samples were examined in accordance to the 2010 World Health Organization criteria. Sperm DNA Fragmentation (DFI) was determined by fluorescence microscopy using terminal deoxynucleotidyl transferase-mediated d-UTP Nick-end Labeling (TUNEL) assay. Statistical analysis was performed using both the t-test for paired samples and the Wilcoxon signed-rank test.</p><p>Results: FSH administration improved DFI in 67% of patients, with an average decrease of 35.4% compared to the baseline. This improvement is more evident in men with basal DFI lower than 17% and in those with FSH basal levels between 2.16 and 4.27 IU/L. In addition, FSH enhanced the gonadal function, increasing the hormones AMH and Inhibin B and semen parameters. Limitation of these results are represented by the absence of a placebo group and of FSHR genotype stratification sub-analysis.</p><p>Conclusion: Recombinant FSH 150 IU is well tolerated and effective in eliciting a significant DFI reduction as well as in improving gonadal function.</p><p>Trial Registration: EUDRACT Number 2010-020196-23. Registred 14 April 2011.</p